ClinVar Miner

Submissions for variant NM_000527.4:c.(?_-1)_(940+1_941-1)del

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genomics Laboratory, Stanford Medicine RCV004598553 SCV005091105 pathogenic Hypercholesterolemia, familial, 1 2022-01-20 criteria provided, single submitter clinical testing This deletion includes exons 1-6 of the LDLR gene. The breakpoints of this event extend beyond the interrogated LDLR region, but additional RefSeq genes are not included in the deletion. Overlapping and similar-sized deletions involving exons 1-6 of the LDLR gene have been previously reported in at least 4 individuals with familial hypercholesterolemia or homozygous familial hypercholesterolemia (Lelli et al., 1991; Sun et al., 1992; Bertolini et al., 2000; Awan et al., 2008). Deletion involving the LDLR gene partially overlapping the deletion identified here has been identified in 2/1, 936 East Asian chromosomes (2/20,002 chromosomes overall) by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Although overlapping deletions have been seen in the general population, their frequency is low enough to be consistent with the prevalence of familial hypercholesterolemia. This deletion removes 6 out of 18 exons of the LDLR gene and is expected to result in a truncated or absent protein product. Loss-of-function is an established mechanism of disease for the LDLR gene. These data were assessed using the ACMG/ClinGen copy number variant interpretation guidelines. In summary, there is sufficient evidence to classify the LDLR exons 1-6 deletion as pathogenic for familial hypercholesterolemia in an autosomal dominant manner based on the information above.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.